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Am J Trop Med Hyg. 2018 Nov;99(5):1336-1341. doi: 10.4269/ajtmh.18-0322.

Trends in C-Reactive Protein, D-Dimer, and Fibrinogen during Therapy for HIV-Associated Multidrug-Resistant Tuberculosis.

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Section of Infectious Disease, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
Department of Epidemiology (Microbial Diseases), Yale University School of Public Health, New Haven, Connecticut.
Department of Internal Medicine, Edendale Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa.


HIV-positive adults on treatment for multi drug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes. To determine whether changes in C-reactive protein (CRP), D-dimer, and fibrinogen were associated with treatment outcome among those with HIV/MDR-TB coinfection, we studied 20 HIV-positive participants for the first 16 weeks of MDR-TB therapy. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. At baseline, all biomarkers were elevated above normal levels, with median CRP 86.15 mg/L (interquartile range [IQR] 29.25-149.32), D-dimer 0.85 µg/mL (IQR 0.34-1.80), and fibrinogen 4.11 g/L (IQR 3.75-6.31). C-reactive protein decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. Five (25%) participants died after a median of 32 days. Older age (median age of 38y among survivors and 54y among deceased, P = 0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, P = 0.02) were significantly associated with death. After adjusting for other measured variables, higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval. Trends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB coinfection.

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